The objective of this study was to investigate the pharmacokinetic profile of tildipirosin (TD) in 24 beagle dogs following intravenous (i.v.) and intramuscular (i.m.) administration, respectively, at 2, 4, and 6 mg/kg. Plasma samples at certain time points (0-14 days) were collected, and the concentrations of drug were quantified by UPLC-MS/MS. Plasma concentration-time data and relevant parameters were described by noncompartmental through WinNonlin 6.4 software. After single i.m. injection at 2, 4, and 6 mg/kg body weight, mean maximum concentration (C max ) was 412.73 ± 76.01, 1,051 ± 323, and 1,061 ± 352 ng/ml, respectively. Mean time to reach C max was 0.36 ± 0.2, 0.08 ± 0.00, and 0.13 ± 0.07 hr after i.m. injection at 2, 4, and 6 mg/kg, respectively. The mean value of T 1/2λz for i.m. administration at doses of 2, 4, and 6 mg/kg was 71.39 ± 28.42, 91 .33 ± 50.02, and 96.43 ± 45.02 hr, respectively. The mean residence times were 63.81 ± 10.96, 35.83 ± 15.13, and 38.18 ± 16.77 hr for doses of 2, 4, and 6 mg/kg, respectively. These pharmacokinetic characteristics after i.m. administration indicated that TD could be rapidly distributed into tissues on account of the high lipid solubility and then released into plasma. In addition, the absolute bioavailability of 2 mg/kg after i.m. injection was 112%. No adverse effects were observed after i.v. and i.m. administration. Tildipirosin (20,

Vrille (Vri), a basic leucine zipper transcription factor, plays important roles in insect circadian clock regulation, tracheal development, proliferation, flight and metamorphosis. Here, Helicoverpa armigera was used as a model to investigate the role of Vri in larval moulting and metamorphosis. Sequence analysis results revealed that H. armigera Vri (HaVri) shares a high amino acid identity with other Lepidoptera Vri homologues. Spatial–temporal expression pattern data showed that HaVri expression was highly abundant in larval moulting and metamorphosis stages and was mainly expressed in the midgut and Malpighian tubule during metamorphosis. HaVri knockdown by RNA interference in the fourth‐instar larvae prevented larval moulting, and HaVri knockdown in the fifth‐instar larvae suppressed midgut remodelling and delayed or blocked metamorphosis. Further studies confirmed that 20‐hydroxyecdysone (20E) activated HaVri expression via its heterodimer receptors, ecdysone receptor (EcRB1) and ultraspiracle protein (USP1), whereas methoprene [juvenile hormone analogue (JHA)] promoted HaVri expression via its intracellular receptor methoprene‐tolerant (Met1). However, 20E and JHA can counteract each other in the activation of HaVri expression. Together, the present results suggested that HaVri was involved in larval moulting and metamorphosis and was regulated by 20E and JHA in H. armigera.

This study aimed to evaluate the absolute bioavailability of cyclosporine in cats by investigating the pharmacokinetic profile after intravenous and oral administration, respectively. Twenty-four clinically healthy cats were enrolled in this study and randomly divided into four groups, namely the intravenous group (3 mg/kg), low oral group (3.5 mg/kg), medium oral group (7 mg/kg), and high oral group (14 mg/kg). Whole blood was obtained at the scheduled time points after a single dose administration and cyclosporine was determined using ultra-performance liquid chromatography–tandem mass spectrometry technology (UPLC-MS/MS). Pharmacokinetic parameters were calculated using the WinNonlin 8.3.4 software via compartmental and non-compartmental models. As a result, the bioavailability values for the low, medium, and high oral groups were 14.64%, 36.98%, and 13.53%, respectively. The nonlinear pharmacokinetic profile was observed in the range from 3.5 mg/kg to 14 mg/kg in cats following oral administration. Whole blood concentrations taken 4 h after oral administration were better correlated with the area under the blood concentration–time curve AUC0–24 with a high regression coefficient (R2 = 0.896). This concentration would be a greater predictor in the following therapeutic drug monitoring. No adverse effect was observed in the whole study process.